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21.
Comments on the suggested use of the progestagen-only Pill (minipill) in breast-feeding women are presented. Progestagens vary with respect to their estrogenic, progestational, and androgenic effects and, therefore, have varying effects on lactation. Megestranol acetate, .5 mg daily, or chlormadinone acetate, .5 mg daily, are without effect on lactation, while norethisterone, 35 mg, decreases the quality and quantity of milk. Thus, it is essential to indicate the specific compounds and dosages of the progestagen-only pill in any statement recommending their use in these women. It is suggested that the pharmacology of all available progestagen-only oral contraceptives be studied in order to determine the 1 with the least potency in estrogenicity or androgenicity. 相似文献
22.
Pharmacokinetics, in-situ absorption and protein binding studies of a new neuroleptic agent centbutindole in rats. 总被引:1,自引:0,他引:1
Manish Issar Shio K Singh Bhrameshwar Mishra Ram C Gupta 《European journal of pharmaceutical sciences》2003,19(2-3):105-113
The present study reports the absorption kinetics, plasma protein binding and pharmacokinetic profile of the centbutindole (I) after i.v. and oral dosing in rats. In addition, an in-situ absorption study was carried out using a closed-loop technique at pH 2.6 and 7.4. The rate of absorption at pH 2.6 was 5-fold less compared to that observed at pH 7.4. In-vitro and in-vivo protein binding (ultra filtration technique) was independent of substrate concentration over a range of 1.25-10.0 microg/ml. Pharmacokinetic parameters of I were determined in male rats after administering a single 4 mg/kg oral dose and 2 mg/kg intravenous dose. The peak serum concentration of I was found to be 50.1 ng/ml at 30 min after oral administration followed by a secondary Cmax of 43.2 ng/ml at 180 min. For the hydroxy metabolite (II), a Cmax of 6.4 ng/ml was measured at 360 min after oral administration of I. After oral dosing an irregular concentration-time profile with secondary peaks was observed for both I and II. The terminal half-lives for I and II after oral dosing were 163 and 263 min, respectively. After intravenous dosing, the levels of I decreased biexponentially with a distribution (t(1/2) alpha) and elimination (t(1/2) beta) half-lives of 5.7 and 128 min, respectively. Comparison of the AUC after oral and intravenous dosing of I indicates that only about 24% of the oral dose reaches the systemic circulation. The limited bioavailability can either be due to the poor solubility of the compound and/or extensive first pass metabolism in the gastrointestinal (GI) tract. Co-administration of polyethylene glycol (PEG) at oral dosing improves solubilization and increases bioavailability. 相似文献
23.
Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days. 总被引:4,自引:0,他引:4
Jame Abraham Manish Agrawal Susan Bakke Ann Rutt Maureen Edgerly Frank M Balis Brigitte Widemann Louis Davis Bharat Damle Daryl Sonnichsen David Lebwohl Susan Bates Herb Kotz Tito Fojo 《Journal of clinical oncology》2003,21(9):1866-1873
PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. 相似文献
24.
A novel approach for immunocontraception by intervention of local cell mediated immunity in the reproductive system by using single intrauterine application of neem oil has been described earlier. The reversible block in fertility was reported to last for 107–180 days in female Wistar rats (Upadhyay et al., 1990. Antifertility effects of neem oil by single intrauterine administration: A novel method of contraception. Proceedings Of The Royal Society Of London B 242, 175–180) and 7–11 months in monkeys (Upadhyay et al., 1994. Long term contraceptive effects of intrauterine neem treatment (IUNT) in bonnet monkeys: An alternative to intrauterine contraceptive devices. Contraception 49, 161–167). The present study, describes the identification and characterization of the biologically active fraction from neem seeds (Azadirachta indica A. Juss. Family Meliaceae), responsible for the above activity in adult female Wistar rats. Initial studies with the mechanically extracted oil and solvent extracts of neem seeds have revealed that the antifertility activity was present in constituents of low to intermediate polarity. A hexane extract of neem seeds was reported to be biologically active (Garg et al., 1994. Comparison of extraction procedures on the immunocontraceptive activity of neem seed extracts. Journal of Ethnopharmacology 22, 87–92). Subsequently, hexane extract was sequentially fractionated through the last active fraction using various separation techniques and tested for antifertility activity at each step. Preparative HPLC was used for isolating individual components of the active fraction in quantities, sufficient for characterization. An analytical HPLC method was developed for standardization of the fraction. The active fraction was identified to be a mixture of six components, which comprises of saturated, mono and di-unsaturated free fatty acids and their methyl esters. Dose response study was performed with the last active fractions. The antifertility activity with the active fraction was reversible in nature and it was completely active until 5% concentration. There was no systemic toxic effect following the administration of the active fraction. This study, for the first time, proposes an active fraction from neem seeds, responsible for long term and reversible blocking of fertility after a single intrauterine administration with high efficacy. 相似文献
25.
26.
Michael A Repka Kavitha Gutta Suneela Prodduturi Manish Munjal Steven P Stodghill 《European journal of pharmaceutics and biopharmaceutics》2005,59(1):189-196
Hot-melt extrusion technology was used to produce thin films containing a model drug, lidocaine, and the cellulosic polymers hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC). Two film formulations were extruded and compared, one containing only HPC and the other containing HPC:HPMC (80:20). Thermal analysis of the films using differential scanning calorimetry (DSC) suggested that the drug existed in the amorphous condition, which was confirmed by wide angle X-ray diffractometry. Sustained release of the drug was observed from both of the polymer matrices. Dissolution profiles suggested that HPMC retarded the drug release from HPC:HPMC (80:20) films. However, the mechanism of drug release from both of the films was predominantly diffusion of the drug through the polymer matrices. Incorporation of HPMC also increased both adhesive strength and work of adhesion as compared to the HPC-only films. 相似文献
27.
Gupta Sumita Mukherjee Aparna Lodha Rakesh Kabra Madhulika Deepak Kishore K. Khadgawat Rajesh Talwar Anjana Kabra Sushil Kumar 《Indian journal of pediatrics》2019,86(11):987-994
Indian Journal of Pediatrics - To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF). Fifty-two CF children (mean... 相似文献
28.
Anna de Waal C. Sarai Racey Robine Donken Kara Plotnikoff Simon Dobson Laurie Smith Troy Grennan Manish Sadarangani Gina Ogilvie 《Canadian journal of public health. Revue canadienne de santé publique》2022,113(5):776
ObjectiveThe aim of this study was to explore the acceptability of bacterial STI vaccines among young HPV-vaccinated Canadian women to inform future vaccine program implementation.MethodsA 20-item cross-sectional questionnaire was administered from June 2019 to June 2020 to HPV-vaccinated participants of the pan-Canadian QUEST cohort. Multivariable logistic regression models assessed interest in chlamydia, syphilis, and gonorrhea vaccines using a priori variables and factors significant in bivariate analysis.ResultsOf the 1092 respondents analyzed, 82% indicated interest in receiving one or more future STI vaccines. Respondents had a median age of 19.6 years (range 16.9–23.4), and 75% of respondents identified as white/European descent. In adjusted analyses, intent to engage in positive health behaviours was associated with vaccine interest for syphilis (OR = 5.76, 95% CI 4.03–8.27), chlamydia (OR = 5.27, 95% CI 3.66–7.63), and gonorrhea (OR = 5.96, 95% CI 4.15–8.60). Willingness to pay for an STI vaccine was also associated with vaccine interest for syphilis (OR = 2.02, 95% CI 1.29–3.19), chlamydia (OR = 2.41, 95% CI 1.50–3.90), and gonorrhea (OR = 2.29, 95% CI 1.44–3.63). Ever having sexual intercourse and identifying as LGBTQ were significantly associated with vaccine interest for all infections, while age and ever being immunosuppressed were not significant in any adjusted models.ConclusionFindings indicate over 80% of participants in a cohort of young HPV-vaccinated Canadian women are interested in receiving future bacterial STI vaccines. Further exploration of STI vaccine acceptability among diverse populations is required to inform future bacterial STI vaccine program implementation.Supplementary InformationThe online version contains supplementary material available at 10.17269/s41997-022-00648-2. 相似文献
29.